Disruption of Cholesterol Homeostasis Triggers Periodontal Inflammation and Alveolar Bone Loss

Overview

Journal Exp Mol Med

Specialties Biochemistry
Molecular Biology

Date 2023 Nov 30

PMID 38036731

Authors

Thanh-Tam Tran

Gyuseok Lee

Yun Hyun Huh

Ki-Ho Chung

Sun Young Lee

Ka Hyon Park

Seung Hee Kwon

Min-Suk Kook

Jang-Soo Chun

Jeong-Tae Koh

Je-Hwang Ryu

Affiliations

Soon will be listed here.

Abstract

Oral diseases exhibit a significant association with metabolic syndrome, including dyslipidemia. However, direct evidence supporting this relationship is lacking, and the involvement of cholesterol metabolism in the pathogenesis of periodontitis (PD) has yet to be determined. In this study, we showed that high cholesterol caused periodontal inflammation in mice. Cholesterol homeostasis in human gingival fibroblasts was disrupted by enhanced uptake through C-X-C motif chemokine ligand 16 (CXCL16), upregulation of cholesterol hydroxylase (CH25H), and the production of 25-hydroxycholesterol (an oxysterol metabolite of CH25H). Retinoid-related orphan receptor α (RORα) mediated the transcriptional upregulation of inflammatory mediators; consequently, PD pathogenesis mechanisms, including alveolar bone loss, were stimulated. Our collective data provided direct evidence that hyperlipidemia is a risk factor for PD and supported that inhibition of the CXCL16-CH25H-RORα axis is a potential treatment mechanism for PD as a systemic disorder manifestation.

Citing Articles

Acceleration of HDL-Mediated Cholesterol Efflux Alleviates Periodontitis.

Tran T, Lee G, Huh Y, Chung K, Lee S, Park K J Dent Res. 2024; 103(11):1109-1118.

PMID: 39311443 PMC: 11653281. DOI: 10.1177/00220345241271075.

References

Luo J, Yang H, Song B . Mechanisms and regulation of cholesterol homeostasis. Nat Rev Mol Cell Biol. 2019; 21(4):225-245. DOI: 10.1038/s41580-019-0190-7. View

Hotamisligil G . Inflammation and metabolic disorders. Nature. 2006; 444(7121):860-7. DOI: 10.1038/nature05485. View

Cekici A, Kantarci A, Hasturk H, Van Dyke T . Inflammatory and immune pathways in the pathogenesis of periodontal disease. Periodontol 2000. 2013; 64(1):57-80. PMC: 4500791. DOI: 10.1111/prd.12002. View

Kang W, Hu Z, Ge S . Healthy and Inflamed Gingival Fibroblasts Differ in Their Inflammatory Response to Porphyromonas gingivalis Lipopolysaccharide. Inflammation. 2016; 39(5):1842-52. DOI: 10.1007/s10753-016-0421-4. View

Nepomuceno R, Pigossi S, Finoti L, Orrico S, Cirelli J, Barros S . Serum lipid levels in patients with periodontal disease: A meta-analysis and meta-regression. J Clin Periodontol. 2017; 44(12):1192-1207. DOI: 10.1111/jcpe.12792. View

Kononen E, Gursoy M, Gursoy U . Periodontitis: A Multifaceted Disease of Tooth-Supporting Tissues. J Clin Med. 2019; 8(8). PMC: 6723779. DOI: 10.3390/jcm8081135. View

Shi J, Fan J, Su Q, Yang Z . Cytokines and Abnormal Glucose and Lipid Metabolism. Front Endocrinol (Lausanne). 2019; 10:703. PMC: 6833922. DOI: 10.3389/fendo.2019.00703. View

Hajishengallis G, Chavakis T . Local and systemic mechanisms linking periodontal disease and inflammatory comorbidities. Nat Rev Immunol. 2021; 21(7):426-440. PMC: 7841384. DOI: 10.1038/s41577-020-00488-6. View

Guillemot-Legris O, Mutemberezi V, Muccioli G . Oxysterols in Metabolic Syndrome: From Bystander Molecules to Bioactive Lipids. Trends Mol Med. 2016; 22(7):594-614. DOI: 10.1016/j.molmed.2016.05.006. View

10.

Abdul Zani I, Stephen S, Mughal N, Russell D, Homer-Vanniasinkam S, Wheatcroft S . Scavenger receptor structure and function in health and disease. Cells. 2015; 4(2):178-201. PMC: 4493455. DOI: 10.3390/cells4020178. View

11.

Williams J, Huang L, Randolph G . Cytokine Circuits in Cardiovascular Disease. Immunity. 2019; 50(4):941-954. PMC: 6924925. DOI: 10.1016/j.immuni.2019.03.007. View

12.

Kinane D, Stathopoulou P, Papapanou P . Periodontal diseases. Nat Rev Dis Primers. 2017; 3:17038. DOI: 10.1038/nrdp.2017.38. View

13.

Stohr J, Barbaresko J, Neuenschwander M, Schlesinger S . Bidirectional association between periodontal disease and diabetes mellitus: a systematic review and meta-analysis of cohort studies. Sci Rep. 2021; 11(1):13686. PMC: 8249442. DOI: 10.1038/s41598-021-93062-6. View

14.

Paul O, Arora P, Mayer M, Chatterjee S . Inflammation in Periodontal Disease: Possible Link to Vascular Disease. Front Physiol. 2021; 11:609614. PMC: 7841426. DOI: 10.3389/fphys.2020.609614. View

15.

Varela-Lopez A, Quiles J, Cordero M, Giampieri F, Bullon P . Oxidative Stress and Dietary Fat Type in Relation to Periodontal Disease. Antioxidants (Basel). 2016; 4(2):322-44. PMC: 4665476. DOI: 10.3390/antiox4020322. View

16.

Aslanian A, Charo I . Targeted disruption of the scavenger receptor and chemokine CXCL16 accelerates atherosclerosis. Circulation. 2006; 114(6):583-90. DOI: 10.1161/CIRCULATIONAHA.105.540583. View

17.

Pirih F, Monajemzadeh S, Singh N, Sinacola R, Shin J, Chen T . Association between metabolic syndrome and periodontitis: The role of lipids, inflammatory cytokines, altered host response, and the microbiome. Periodontol 2000. 2021; 87(1):50-75. PMC: 8457155. DOI: 10.1111/prd.12379. View

18.

Wu L, Parhofer K . Diabetic dyslipidemia. Metabolism. 2014; 63(12):1469-79. DOI: 10.1016/j.metabol.2014.08.010. View

19.

Rader D, Hovingh G . HDL and cardiovascular disease. Lancet. 2014; 384(9943):618-625. DOI: 10.1016/S0140-6736(14)61217-4. View

20.

Bui F, Almeida-da-Silva C, Huynh B, Trinh A, Liu J, Woodward J . Association between periodontal pathogens and systemic disease. Biomed J. 2019; 42(1):27-35. PMC: 6468093. DOI: 10.1016/j.bj.2018.12.001. View